Our study offers original in vitro evidence that arginine depletion may stimulate the PI3K/AKT pathway in MM cells and protect from cell death, as it reduced the pro-apoptotic impact of the first-in-class PI bortezomib, an effect possibly mediated, at least in part, by the inhibitory phosphorylation of the BH3-only protein BAD. Here, BAD is linked to Miyoshi myopathy.